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Integration of G protein signals by extracellular signal‐regulated protein kinases in SK‐N‐MC neuroepithelioma cells
Author(s) -
Chan Anthony S. L.,
Yeung Wendy W. S.,
Wong Yung H.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03304.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , kinase , p38 mitogen activated protein kinases , g protein coupled receptor , phosphorylation , extracellular , receptor , proto oncogene tyrosine protein kinase src , signal transduction , mitogen activated protein kinase , chemistry , biology , biochemistry
Mammalian cells often receive multiple extracellular stimuli under physiological conditions, and the various signaling inputs have to be integrated for the processing of complex biological responses. G protein‐coupled receptors (GPCRs) are critical players in converting extracellular stimuli into intracellular signals. In this report, we examined the integration of different GPCR signals by mitogen‐activated protein kinases (MAPKs) using the SK‐N‐MC human brain neuroepithelioma cells as a neuronal model. Stimulation of the G i ‐coupled neuropeptide Y 1 and G q ‐coupled muscarinic M 1 acetylcholine receptors, but not the G s ‐coupled dopamine D 1 receptor, led to the activation of extracellular signal‐regulated kinase (ERK). All three receptors were also capable of stimulating c‐Jun NH 2 ‐terminal kinases (JNK) and p38 MAPK. The G i ‐mediated ERK activation was completely suppressed upon inhibition of Src tyrosine kinases by PP1, while the G q ‐induced response was suppressed by both PP1 and the Ca 2+ chelator, BAPTA‐AM. In contrast, activations of JNK and p38 by G s ‐, G i ‐, and G q ‐coupled receptors were sensitive to PP1 and BAPTA‐AM pretreatments. Simultaneous stimulation of G i ‐ and G q ‐coupled receptors resulted in the synergistic activation of ERK, but not JNK or p38 MAPK. The G i /G q ‐induced synergistic ERK activation was PTX‐sensitive, and appeared to be a co‐operative effect between Ca 2+ and Src family tyrosine kinases. Enhanced ERK activation was associated with an increase in CREB phosphorylation, while the JNK and p38‐responsive transcription factor ATF‐2 was weakly enhanced upon G i /G q ‐induction. This report provides evidence that G protein signals can be integrated at the level of MAPK, resulting in differential effects on ERK, JNK and p38 MAPK in SK‐N‐MC cells.